The sympathetic ganglion is a good model system for the study of neuronal synaptic transmission. We have demonstrated several means which alter the effectiveness of synaptic transmission in this preparation including: 1) preganglionic tetany, 2) alpha-receptors, and 3) adenosine receptor activation. Our four year objective is to study the fundamental mechanisms by which these processes change synaptic efficacy. It is clear that a quantitative study of ion conductance mechanisms in the sympathetic neuron is required since conductance processes form much of the substrate for synaptic modulation. This requires knowledge of the electrotonic and anatomical structure of the neuron which will be studied by intracellular injection of current and dye. We will develop techniques for low noise recording of responses to synaptic and current injections. Ultimately we intend to determine the kinetics of single Ca++ channels and the effects of specific agonists on these channels. It is likely that catecholamines, purines, and even peptides act on presynaptic receptors in sympathetic ganglia in the same way they act at comparable structures in the brain. we intend to better define by both intracellular and extracellular recording techniques, the physiology and pharmacology of receptor-mediated neuromodulation.